Compliant osteosynthesis fixation plate

ABSTRACT

A bendable polymer tissue fixation device suitable to be implanted into a living body, consisting of a highly porous body, made from a polymer, the porous body having a plurality of pores, such that the device is capable of being smoothly bent, wherein the bending collapses a portion of the pores to form a radius curve, and the polymer fixation device is rigid enough to protect a tissue from shifting. Preferably, the polymer fixation device may be capable of being gradually resorbed by said living body. In one embodiment, the polymer fixation device consists of a plurality of layers distinguishable by various characteristics, such as structural or chemical properties. In another embodiment, the polymer fixation device may feature additional materials which serve to reinforce or otherwise alter the structure or physical characteristics of the device, or alternatively the additional materials serve to deliver therapies to the living being.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation-In-Part of U.S. patent applicationSer. No. 10/619721, filed on Jul. 15, 2003, entitled CompliantOsteosynthesis Fixation Plate which is assigned to the same assignee asthis invention, and whose disclosure is incorporated by referenceherein.

FIELD OF THE INVENTION

The invention generally relates to prosthetic implants, specificallyrelating to resorbable prosthetic implants. The invention moreparticularly concerns a resorbable osteosynthesis fixation plate.Specifically, an implant for joining tissue or bone fragments of thecranium, face and other plastic/reconstructive procedures.

BACKGROUND OF THE INVENTION

Rigid internal fixation has been indicated for treatment of defects ofthe mammalian skeletal system for decades. Although external fixationsuch as plaster and splints have been used to stabilize the skeletonsince ancient times, it was not until the emergence of steel wire in thenineteenth century that a practical method for treating non-isolatablebone fragments such as those found in craniomaxillofacial repairsituations was developed.

A great advancement in skeletal fixation occurred in the late 1950s withthe introduction of metallic plate systems. By securing the plate to theindividual bone components with screws, this relatively simple deviceprevented fragment motility commonly encountered with wire-stabilizedrepair. These plates are generally sheets of metal that are fenestratedat various points along their lengths for fastening by screw. Over theyears, metallic plate systems have become miniaturized and morebiocompatible. Initially made from stainless steel, subsequent alloys,which include Vitallium® and titanium, were developed allowing forimproved strength and rigidity. A panoply of geometric configurations isavailable to meet nearly every conceivable bone fixation need. Theapplication of metallic materials has greatly improved aestheticoutcomes and has enabled earlier and more complete surgicalreconstructions.

The search for improved fixation implants has lead to the development ofa plethora of prostheses for utilization in surgical procedures, forexample, fiber reinforced sheets to prevent hernias, bone plates toallow healing of bones after fracture and skull plates for use aftercranial surgery. In particular, bone fixation plate and skull plateimplants are utilized in a manner such that their placement may preventbone fragment movement relative to the remainder of the bone. See, e.g.,U.S. Pat. No. 3,741,205. The construction of these prostheses hashistorically been of some metal or metal alloy, e.g., surgical stainlesssteel, titanium, or Vitallium®. See, e.g., U.S. Pat. No. 6,344,042.These metal prostheses have the desired strength and rigidity toproperly stabilize the area and allow the healing process to occurunimpeded by fragment and/or bone shifting. The stabilization may beexternal to the body, by use of a scaffold of rods and braces (see,e.g., U.S. Pat. No. 3,877,424) or alternatively, implanted internallyand fastened to the bone via a securing means, such as cementing,medical staples, pins, nails, tacks, screws or clamps. See, e.g., U.S.Pat. Nos. 5,201,733; 6,454,770; 6,336,930.

Metal plates to be utilized as prostheses to immobilize bone fragmentshave the ability to be customized to fit the unique contours of eachpatient. Customization of the prosthesis is accomplished by twisting andbending the plates to fit the surgical site. Despite the utility ofmetallic plate systems, their use is not without problems. Multiplebending attempts may be required to achieve a desired fit, potentiallyfatiguing the metal. Furthermore, an extended customization and shapingprocess may lead to higher risk for the patient, due to a protractedperiod while under anesthesia, as well as increased opportunity forinfection.

The consequences of long-term metal implants over a fifty to seventyyear period are not known. Particles from these devices have beenisolated in very distant organs such as the liver and the lung. Traceamounts of aluminum and nickel have been found in tissues surroundingimplants thought to be composed of pure titanium. Metal plates have thedrawback of remaining in place long after the healing process iscomplete, unless removed through a second invasive procedure. Thisintransience may be harmful where there is a need for continued bonegrowth and that growth is restrained by the implant, e.g., a child'sskull must be capable of continued growth through development, and ametal skull plate, if left in place after cranial surgery, wouldinterfere with developmental growth. Other postoperative complicationsfrom metallic plating systems include: visibility or palpability,hardware loosening with resulting extrusion (e.g. “screw backout”),temperature sensitivity to cold, screw migration and maxillarysinusitis, bone atrophy or osteopenia caused by stress shielding andcorrosion, interference with radiographic imaging and radiation therapy,allergic reactions, intracranial migration in cranio-orbital surgery,and the possibility of causing growth restriction of the craniofacialskeleton on pediatric patients. Additionally, a metal prosthesis, if notremoved after healing, may over time corrode or allow the leaching ofmetals to other locations of the body. For these reasons, the pursuit ofother fixation technology has continued.

In order to overcome some or all of the drawbacks of metal implants,considerable attention has been given to the field of biodegradable(absorbable, resorbable) prostheses. These prostheses are capable ofprotecting the injury site, while still allowing the healing process tooccur; however the resorbable nature of the prostheses allows theprostheses to remain in place only as long as would be needed tocomplete the healing process. The resorption of the implant obviates theneed for a second surgical procedure to remove the implant, as might berequired for a non-absorbable prosthesis, thereby reducing opportunityfor infection or other complications. Additionally, any problemscommonly associated with metal implants that may also be associated withresorbable implants, such as bone atrophy, would be transient, as theproblem would not persist beyond the absorption of the implant.

The use of resorbable materials to form an implantable prosthesis is notnew. See, e.g., U.S. Pat. No. 3,739,773. Bioresorbable internal fixationdevices have been available for years principally as pins, plugs,screws, tacks and suture anchors. In 1996, the United States Food andDrug Administration approved the first bioresorbable internal fixationsystem for craniomaxillofacial indications (LactoSorb®, Walter LorenzSurgical, Inc., Jacksonville, Fla.). Available in a variety of screws,panels and plate designs, the material is a non-porous amorphouscopolymer of L-lactic and glycolic acid in a ratio of 82:18 andengineered to completely resorb in 9 to 15 months following placement.The material has manufactured fenestration points located throughout thedevice to allow for screw fixation to bone. Other resorbable materialsnow available commercially include Synthes® and MacroPoreFX™ fixationplates.

Prior art discloses that bioresorbable internal fixation plates can bemanufactured by injection molding or compression molding techniques. Forinjection molding, a mold of the desired plate is first fabricated. Thedesired polymer is then heated significantly above its glass transitiontemperature until its viscosity is low enough to allow the polymer toflow. As this is occurring, a screw carries the molten polymer into themold where it is allowed to cool below its glass transition temperature.The polymer is now solidified to the shape of the mold. The advantage toinjection molding is that extremely intricate mold designs can beproduced. One disadvantage of injection molding, however, is that thepolymer may undergo a relatively long heat cycle, which breaks down themolecular weight of the polymer, thereby, affecting material strength aswell as degradation characteristics. Another major disadvantage toinjection molding is that there will usually be a certain amount ofinherent stress within the plate due to freezing the polymer in placeprior to it obtaining the orientation of lowest energy. Over time, or ifthe plate is heated prior to use, it will deform in order to relieve thestress in the part. In the case of heat application, the screw holes ofthe plate have been shown to become distorted causing some screw pointsto become unusable or preventing proper thread contact and alignment.Annealing may be used to help prevent this deformation from occurring.Annealing requires holding the plate in place while heating it above itsglass transition temperature and waiting for the stress to relieve. Thisis an additional heating step and can lengthen a manufacturing processor further break down the molecular weight of the polymer.

Another method of thermally forming a polymer into a resorbable fixationplate is compression molding. Under this method, a mold is firstproduced and placed between hot platens. The two mold halves areseparated and polymer is placed into the mold. Compressive pressure isapplied to the mold and it is then heated above the glass transitiontemperature of the polymer. The polymer will eventually start to flow asthe mold heats up and the material will take the shape of the mold. Theadvantage to this method is that the fixation plates incur very littlemolded-in stress because the polymer only has a relatively shortdistance to move. Disadvantages to this method include an even longerheating cycle than injection molding, a slow process that is difficultto use on a large scale, and a process that may require machining theholes into the fixation plate as a second operation.

The materials derived from ordinary thermal molding techniques(injection and compression molding) are not flexible at roomtemperature. Generally, the resorbable craniomaxillofacial productscurrently on the market are not deformable at room temperature and mustbe heated prior to implantation to adapt the device to the contours ofthe wound site. As the patients often vary in size, and because the bonesurfaces are not flat, during implantation there exists a need to fitthe prosthesis to the particular contours of each patient. Varioustechniques may be utilized to heat the prosthesis (e.g. exposure to hotair, immersion in hot liquid, exposure to radiation or exposure to someother heating medium) to a temperature above the glass transition point,but below the melting point; thereby making the prosthesis temporarilyflexible, and allowing it to be fitted to an individual by bending,either by hand or with special bending tools. See, e.g., U.S. Pat. No.5,290,281. After heating, the physician has only a limited amount oftime, often just seconds, in which to accomplish the bending. Dependingon the thickness of the plate, this period of malleability can be asshort as two to three seconds causing the practitioner in many instancesto expend considerable time to reheat and reshape the material severaltimes while bending to achieve proper conformity. This additional timeincreases anesthesia requirements and operating room time and increasesthe potential of infection. See U.S. Pat. No. 6,332,884 for a prosthesisthat turns to a clear solid while heated above its glass transitiontemperature, and reverts back to an opaque solid when cooled below theglass transition temperature, giving a visual indication to thephysician about the status of the prosthesis' flexibility. The limitedperiod of time available for bending of the prosthesis requiresdexterity and care by the physician to create a shape that is adequatefor use with each individual. The repeated heating, if necessary, toallow careful molding of the prosthesis adds to the time and complexityand cost of the procedure, further increasing the risk to the patient.Furthermore, if the prosthesis is not properly heated above the glasstransition temperature as required for flexibility, and is bent whilebelow the glass transition temperature, then the prosthesis will remaininflexible or be rather brittle, and likely develop cracks and/ormicro-cracks upon bending.

In U.S. Pat. No. 6,221,075, there is disclosed a polymer tissue fixationdevice that may be deformed at room temperature. The ability of thepolymer to be deformed without heating is made possible by an additionalmanufacturing step incorporated into the thermal molding techniquesdescribed above, where the polymer material is oriented with an uni-and/or biaxial solid state deformation process. The solid statedeformation process orients the molecules of the polymer, so that roomtemperature bending is possible without substantial damage or breaking.The deformation process adds to the cost of manufacturing the tissuefixation device, adding to required labor and time of manufacture. Inorder to avoid unwanted bending or warping of the device while exposedto temperatures above the glass transition point but below the meltingpoint, the device must be maintained at elevated temperature afterdeformation to allow stress relief of the polymer molecules. After thedeformation step or stress relief step, any further modifications ormachining, such as holes for fastening devices, must be created beforeuse, such as by drilling.

Walter et al. in U.S. Pat. No. 6,203,573, disclose molded, biodegradableporous polymeric implant materials having a uniform pore sizedistribution. The materials can be molded into implants of any desiredsize and shape without loss of uniformity of pore size distribution. Thematerial may be hand-shaped when warmed to body temperatures, and morepreferably when warmed to at least about 45 degree C. and morepreferably to at least about 50 degree C. Once at an elevatedtemperature, the implant material can be further hand-shaped to fit thedefect into which it is placed and fit the desired shape for the regrowntissue.

A need, therefore exists for an internal fixation device that can beresorbed by the body over time, yet provide sufficient strength toprevent bone fragment motility over the healing period necessary fornatural repair. Furthermore, the device should be capable of manualdeformation at room temperature to fit the unique shape of eachindividual patient without the use of heat or chemical manipulation,wherein the deformation may occur by bending or application of acompressive force. Also the device should be capable of resisting theformation of micro-cracks caused by shaping, or distortions caused bythe introduction of fastening techniques known in the art.

A prosthesis as described above would have the benefits of ease of usein surgery, along with the associated benefit for the patient ofreducing the total time under anesthesia, and minimizing the risk ofinfection for the patient.

In U.S. Pat. Nos. 4,966,599 and 5,413,577, Pollock discloses a set ofpre-formed bone plates, to be manufactured as a kit. The use of anindividual bone plate, comprising one of many in the kit, will stillrequire final shaping by bending or crimping of the plates while thepatient is undergoing surgery. Pollock has taken an approach to minimizethe amount of time required to customize the implant by manufacturingmany plates, encompassing a plurality of generic shapes and sizes, suchthat only minor customization by bending of the appropriate prosthesiswould be required. A multi-piece kit, such as described by Pollock,would necessarily result in waste as the unused sizes and shapes of thekit would be discarded as not being appropriate for the specificpatient's needs.

In U.S. Pat. No. 4,186,448, Brekke describes the use of a porous body,made of biodegradable material, to fill or cover a bone void. Thismaterial includes interconnected, randomly positioned, randomly shapedand randomly sized voids extending throughout the mass of the bodymember. The voids promote the penetration of blood into the prosthesisand aid healing through the facilitation of tissue and/or bone growthinto the prosthesis. The prosthesis as described promotes tissueingrowth and is replaced by new bone upon resorption.

The use of a resorbable prosthesis that serves as a barrier to cellpermeability, while allowing bone wound or void healing is disclosed byHayes et al. in U.S. Pat. No. 6,031,148, and also by Brekke et al. inU.S. Pat. No. 5,855,608. Hayes' prosthetic material serves as a pliablebarrier to cells, acting to prevent soft tissue growth in areas wherebone growth is desired. The Hayes patent discloses the pliableprosthesis having a matrix that is sufficiently open to allowinfiltration of blood and subsequent interconnection of ingrowing tissuethrough the open spaces. Brekke discloses a resorbable implant that iscapable of serving as a barrier to isolate one form of tissue (i.e.bone) from another form of tissue (i.e. soft tissue). Once implanted,the barrier prosthesis would serve to protect a void or wound in onetissue (the bone) from encroachment by the adjoining (soft) tissue,which would otherwise grow unobstructed into the void, precluding thevoid from proper repair with the original type of (bone) tissue.

In EPA 0 274 898, Hinsch discloses a foam-like, resorbable, plasticmaterial, incorporating textile reinforcing elements made fromresorbable plastic embedded in an open-cell plastic matrix, theopen-cell matrix formed by a vacuum, freeze drying process. Theapplication disclosure includes tables demonstrating how the tensilestrength of the implant increases upon addition of the textilereinforcing elements. This increased tensile strength results in animplant that is more resistant to pulling and tearing forces. One of thestated objectives of the invention is to have an open cell structure topermit the growing in of cells and blood vessels, yet still retainadequate tensile strength to serve as an implant. According to thedisclosure, the pores must be of sufficient average size to allow theingrowth of cells and blood vessels.

The aforementioned application EPA 0 274 898 (Hinsch), as well as U.S.Pat. No. 4,186,448 (Brekke), U.S. Pat. No. 6,031,148 (Hayes) and U.S.Pat. No. 5,855,608 (Brekke) disclose resorbable prostheses used to fillor cover tissue voids, relying on the formation of new bone and tissuewithin the implant. None of these disclosures anticipate the need of aprosthesis that conforms to a surgical site via collapse of pores and isutilized to anchor tissue fragments together.

The use of composites in prostheses has been used to improve bothmechanical and biological properties. In PCT application WO 86/00533,for example, Leenslag discloses a composite of fiber material, which mayor may not be biodegradable, incorporated in a porous matrix of abiodegradable organic polymer material. The material as described byLeenslag is suitable for repair or replacement of torn bony material,the term bony material as used therein referring to a damaged meniscus,not to a wound in a bone as contemplated by the subject invention. Thedesign of the prosthesis is such that it requires rapid ingrowth oftissue and vessels as part of its function.

Bowman et al., in U.S. Patent Application Publication No. US2002/0127265 A1, describes a biocompatible tissue repair stimulatingimplant or “scaffold” device. The application discloses an implant thatfacilitates cellular ingrowth, by the open cell foam structure of thepolymer, as well as by the delivery of tissue growth stimulatingcompounds as biological agents within the device. The implant asdescribed may incorporate at least one layer of a mesh or weave offibers to lend mechanical support to the device, in order to enable thedevice to be handled in the operating room prior to and duringimplantation, to enable the implant to resist suture pull through, andto enable the foam device to withstand stresses placed upon it whileimplanted. This compound implant of foam and fiber reinforcement isimplanted with the aim of encouraging tissue ingrowth into the implant,such that as the device is reabsorbed, tissue growth penetrates into thedevice.

Both the Leenslag patent and the Bowman application are for devicesoperating in a manner similar to the aforementioned devices disclosed byEPA 0 274 898, U.S. Pat. No. 4,186,448, U.S. Pat. No. 6,031,148 and U.S.Pat. No. 5,855,608, in that they function as a void filler or tissuereplacement.

An implantable, bioresorbable membrane used to allow healing of a tissuedefect site is disclosed by Yoon et al. in U.S. Pat. No. 5,948,020. Asdescribed therein, the membrane serves to isolate a tissue defect sitefrom encroachment by adjoining tissue while allowing the wound to heal.The implant may also incorporate woven or knitted fabric made ofbioresorbable fibers as a support embedded in a bioresorbable porouspolymer matrix. To achieve sufficient malleability and dimensionalstability, as well as to avoid prior art, the patent discloses animplant whose surfaces have been heated above the glass transitiontemperature to 150 C and forcing a plate with 20 protrusions/cm² intothe already porous device (the embossing step).

Vyakarnum in U.S. Pat. No. 6,306,424 discloses an implant useful as atissue scaffold, for repair or regeneration of tissue havingarchitectural gradients (e.g. bone, cartilage, and skin), wherein theimplant relies on gradients that mimic the histologic pattern of thetissues into which it is implanted.

There exists a need for an implantable, bioabsorbable prosthesis that iscapable of being customized quickly, effectively and easily for theparticular needs of each patient. The prosthesis should be capable ofbeing fastened quickly and easily by a variety of fastening methodsknown in the art, including the use of staples, sutures, adhesives,nails, tacks, pins or clamps. The prosthesis must allow customization byresponding to bending and compressive forces by smoothly bending andholding the desired shape, rather than cracking or breaking suddenly.The customization process should be simple, without requiringspecialized tools or heating, thereby saving time and cost in theoperation, as well as minimizing risk to the patient from prolongedexposure to infection and anesthesia. The prosthesis should allow thephysician to make the customization in situ, while in the surgery suite,even while partially implanted. Furthermore, the absorbable prosthesisshould be rigid enough to serve to isolate and protect the tissue fromshifting. The prosthesis should be capable of being fully absorbed afterthe healing process has completed.

It is the intent of this invention to overcome these and othershortcomings of the prior art.

SUMMARY OF THE INVENTION

The present invention takes advantage of the porous structure of theprosthesis that allows deformation of the device without cracking orbreaking of the structure. When bending pressure, for example, isapplied, individual pores will collapse, allowing the smooth bending ofthe prosthesis in a radius, rather than a sudden collapse of thematerial as the prosthesis breaks. Similarly, if compressive force isapplied, a portion of the pores may collapse, allowing the prosthesis toconform to the shape of the tissue it is pressed against, whilemaintaining the structural rigidity of the device.

While allowing the flexibility to be custom fit to the patient's tissuecontours at room temperature in the operating field without specialtools, the prosthesis retains enough structural rigidity and strength tolend structural support and protect a healing wound of a patient, e.g.,to serve as a tissue or bone fixation device, a skull plate, or otherprosthesis requiring structural rigidity. By altering the construction,such as varying the pore size and number or incorporating reinforcementmaterials, the physical characteristics of the prosthesis can bealtered. In this fashion, a tissue fixation device, e.g., a bone plate,that is more compliant and having controlled structural stiffness due toincorporated pores may be manufactured. A tissue fixation device asdescribed may be useful as a skull plate for example, where less flexingor stress is to be expected. Alternatively, by reducing the size andnumber of pores, a more rigid, and less compliant plate can bemanufactured. Such a prosthesis would be more suitable for higher stressuses, including immobilizing bone fragments for broken ribs, pelvis,arms or legs as non-limiting examples.

The present invention is distinguishable from the prior art of poroustissue replacement devices, as the tissue replacement devices of theprior art serve to replace tissue temporarily, even so much as mimickingthe tissue architecture replaced, and encourage the ingrowth of bloodand tissue to allow new tissue growth to replace the bioerodingprosthesis. In contradistinction, the present invention serves toimmobilize or hold two tissue areas together, functioning as atissue-joining device, and does not require the ingrowth of new tissueas the device bioerodes. The device of the present invention is capableof being bent or altered without requiring any extraneous steps, such asheating or embossing of the device.

These and other objects of this invention are achieved by providing abiodegradable prosthesis, the prosthesis being made of a porous polymerfoam material or alternatively a composite of a porous polymer foammaterial and a reinforcing material. The prosthesis being capable ofroom temperature bending, yet retaining sufficient rigidity and strengthto lend structural support and allow healing while in use. The uniqueuse of pores within the current invention provides advantages overpreviously existing solid polymer and metal bone fixation plates, suchas:

-   -   1) Flexibility over a wide range of temperatures, including room        temperature.    -   2) Ability to be penetrated with fastening devices (e.g., pins,        needles, tacks, screws, etc.) without preformed holes.    -   3) Ability to be sutured through its thickness and resist suture        pull-through.    -   4) Pores allow for superior anchorage when using        glues/adhesives.    -   5) Ability to be cut and shaped using surgical scissors.    -   6) Ability to punch shapes out of large sheets of material.    -   7) Ability to deliver biologically active agents impregnated        within the polymer of the prosthesis.    -   8) Ability to deliver biologically active agents impregnated        within the pores of the prosthesis.    -   9) Ability to be impregnated with structural components.    -   10) Ability to be formed as a multi-phasic device.    -   11) Ability to be formed as a gradient device.    -   12) Mass of device can be modified by changes in porosity and/or        addition of structural components.    -   13) Rigidity of device can be modified by changes in porosity        and/or structural components.    -   14) Device can be bent or shaped without deformation of        preexisting anchorage holes.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1(A) Perspective view of prosthetic material shaped as arectangular bone plate having regular, ordered pores; (B) perspectiveview of prosthetic material shaped as a rectangular bone plate havingirregular, random pores.

FIG. 2(A) Cross-section view of the prosthesis showing regular, orderedpores; (B) cross-section view of the prosthesis having regular, orderedpores showing the prosthesis being bent, along with the resultingcompression and subsequent collapse of pores on inside portion of curve;(C) cross-section of prosthesis having a porous layer and a solid ornearly solid layer; (D) cross-section view of the prosthesis having aporous layer and a solid or nearly solid layer, showing the prosthesisas it is being bent, along with the resulting compression and subsequentcollapse of pores on inside portion of curve, and smooth bend of solidor nearly solid layer; (E) cross-section view of the prosthesis having aporous layer, a solid or nearly solid layer, and a second porous layer;(F) cross-section of prosthesis having a porous layer, a solid or nearlysolid layer, and a second porous layer, showing the prosthesisexperiencing multiple bending forces, along with the resultingcompression of pores on inside portions of the curves, and smoothbending of solid or nearly solid layer.

FIG. 3(A) Cross-section view of the prosthesis showing porous zones, and(B) cross-section of prosthesis under compressive force, showingcollapse of a portion of a zone of pores to conform to shape pressedagainst, and (C) cross-section of prosthesis being bent, showingcompression and subsequent collapse of pores on inside portion of curve.

FIG. 4 Perspective and partial cutaway view of suture and otherfastening devices penetrating through the prosthesis.

FIG. 5 Cross-section view of the prosthesis having a random, irregular,porous structure and also having particulate material or biologicallyactive agents.

FIG. 6(A) Cutaway perspective view of the prosthesis bone plate havingat least one reinforcing fiber arranged randomly throughout theprosthesis; (B) cutaway perspective view of the prosthesis bone platehaving a reinforcing weave or mesh. For simplicity of drawing, theporous nature of the material is not depicted.

FIG. 7 (Prior Art) Cross-sectional views of (A) a solid polymer boneplate as known in the prior art, and (B) a solid polymer bone plate,known in the prior art, as a bending force is applied at a temperatureless than that of the glass transition temperature for the polymer.

FIG. 8 Instructional depictions of a beam in (A) an unbent condition,and (B) a bent condition.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The object of the invention is an implantable prosthesis, constructed ofa porous, resorbable, polymer material. The material comprising theprosthesis or device (as used herein, the terms prosthesis and deviceare used interchangeably) is a resorbable polymer that is biocompatiblewith the systems of a living being. The construction of the prosthesisis such that it is to be capable of easily being shaped. The shaping mayoccur in a variety of manners, such as by bending or compressing toconform to a desired shape without requiring any source of heating orspecial tools, and upon removal of the bending or shaping force, theprosthesis will remain in the exact shape, or nearly so; thus enablingthe prosthesis to fit the unique contours of each patient. Despite beingeasily manipulated by hand, the prosthesis remains rigid and strongenough to lend structural support, and allows protection to the wound ofa living being while the healing process occurs. The device has severaladvantages over metal prostheses, including the resorbable nature of theprosthesis, which obviates the need for a second invasive surgery toremove the device, also the ability to be shaped without the need forspecial tools and/or equipment.

The prosthesis may be sterilized by any low temperature methods known inthe art (e.g. exposure to ethylene oxide, hydrogen peroxide gas plasma,e-beam irradiation or gamma irradiation). The sterilization minimizesthe opportunity of infection to occur as a result of the implant.

In the preferred embodiment of the invention, the porous prosthesis ismanufactured from a resorbable material. The resorption rates ofresorbable polymers can be controlled by varying the polymer material,molecular weight, additives, processing, and sterilization. Resorptionrates can be adjusted to be shorter for applications that requiremechanical strength for only a short period of time or longer forapplications that require mechanical strength to be present for a longerduration. Examples of resorbable polymers that can be used to form theprosthesis are shown in following Table 1. These materials are onlyrepresentative of the materials and combinations of materials, which canbe used as prosthetic material. TABLE 1 Examples Bioresorbable Polymersfor Construction of the Device of the Current Invention: AlginateAliphatic polyesters Cellulose Chitin Chitosan Collagen Types 1 to 20Native fibrous Soluble Reconstituted fibrous Recombinant derivedCopolymers of glycolide Copolymers of lactide Elastin FibrinGlycolide/l-lactide copolymers (PGA/PLLA) Glycolide/trimethylenecarbonate copolymers (PGA/TMC) GlycosaminoglycansLactide/tetramethylglycolide copolymers Lactide/trimethylene carbonatecopolymers Lactide/ε-caprolactone copolymers Lactide/σ-valerolactonecopolymers L-lactide/dl-lactide copolymers Methyl methacrylate-N-vinylpyrrolidone copolymers Modified proteins Nylon-2 PHBA/γ-hydroxyvaleratecopolymers (PHBA/HVA) PLA/polyethylene oxide copolymers PLA-polyethyleneoxide (PELA) Poly (amino acids) Poly (trimethylene carbonates) Polyhydroxyalkanoate polymers (PHA) Poly(alklyene oxalates) Poly(butylenediglycolate) Poly(hydroxy butyrate) (PHB) Poly(n-vinyl pyrrolidone)Poly(ortho esters) Polyalkyl-2-cyanoacrylates PolyanhydridesPolycyanoacrylates Polydepsipeptides Polydihydropyrans Poly-dl-lactide(PDLLA) Polyesteramides Polyesters of oxalic acid Polyglycolide (PGA)Polyiminocarbonates Polylactides (PLA) Poly-l-lactide (PLLA)Polyorthoesters Poly-p-dioxanone (PDO) Polypeptides PolyphosphazenesPolysaccharides Polyurethanes (PU) Polyvinyl alcohol (PVA)Poly-β-hydroxypropionate (PHPA) Poly-β-hydroxybutyrate (PBA)Poly-σ-valerolactone Poly-β-alkanoic acids Poly-β-malic acid (PMLA)Poly-ε-caprolactone (PCL) Pseudo-Poly(Amino Acids) Starch Trimethylenecarbonate (TMC) Tyrosine based polymers

Two exemplary processes which may be used for making the presentresorbable porous polymeric fixation plate are the “plasticized meltflow” or PMF, and “phase separation polymer concentration” or PSPC.

In an embodiment created through the PMF process, the nucleating agent,if any, can be mixed into a gas-permeated plasticized polymer. The gas(e.g. air, oxygen, carbon dioxide, nitrogen, argon, or any inert gas,including combinations thereof) trapped within the polymer begins toexpand as the pressure external to the polymer is reduced. As the gasexpands it attempts to create uniformly dispersed homogeneous sphericalpores. When a nucleating agent is present, the growth of the pores maybe disrupted as the walls defining the pores thin to the point that thenucleating agent begins to protrude. In this case, the nucleating agentmay act as a “modeling agent”. As the gas continues to expand themodeling agent particles begin to interfere with each other and/or theexpanding pore walls, and force the pore to take on an irregular shape.

In an embodiment created through the PSPC process, a modeling agent mayoptionally be dispersed within a polymer solvent solution. In thepractice of the PSPC process, the temperature of the mixture is lowereduntil crystals form within the solution. As the crystals grow they forcethe polymer into a smaller and smaller area similar to the expanding gasin the PMF process. The growth of the crystals may be disrupted if theycome in contact with the optionally added modeling agent. The modelingthen occurs as the crystals continue to grow and press the modelingagent particles in contact with each other and the crystals are thusforced to grow around the particles in an irregular fashion. Aftersolidification vacuum or leaching, a chilled non-solvent removes thesolvent crystals.

The pore characteristics of devices created through the PMF and PSPCprocess may be controlled, with respect to pore size, shape, andpattern. It is recognized that the pores of the device may bemanufactured having pores created in a particular shape, whether regular(e.g., columnar, tubular, cuboidal, spheroidal, etc.) or irregular.Furthermore, the pores may be arranged in an ordered manner or randommanner. That is, an ordered arrangement of the pores exists where thereis a predictable repeating pattern to the pore arrangement. Similarly,pores arranged in a random manner do not have a predictable porearrangement. As an example, a regular ordered pore may be a columnarshape, where the columnar pores are substantially parallel inorientation. Alternatively, a regular, random construction of the poresmay be created where there are columnar pores, but not alignedsubstantially parallel in orientation, rather are randomly oriented.

In those embodiments incorporating a modeling agent, the porosity, poresurface texture and geometry of the matrix may be controlled by varyingthe ratio of polymer to modeling agent in the PMF and PSPC processes;wherein the matrix is polymer, molding agent and porosity combined. Lowpolymer constituent concentrations combined with longer processing timesallows the growth of large pores, thereby affecting mechanical andphysical properties. The rate at which the pores grow (via gas expansionor crystal growth, as appropriate) can determine where in the polymermass the modeling agent is located. Slow growth of pores allows themodeling agent to migrate within the thinning polymer walls and remaincovered or encapsulated. Rapid expansion of the pores does not allowsufficient time for the modeling agent to migrate within the wallsresulting in partial exposures of the modeling agent. The modeling agentmay also control physical and biologic properties. For example, theincorporation of high modulus strengthening components (e.g., polymers,ceramics or metallics) in various forms (e.g., particulate, fiber,whisker, etc.) as the modeling agent will affect the strength andtoughness of the resulting structure.

The modeling agent does not just affect mechanical properties, butrather can serve multiple purposes, which may include but are notlimited to:

-   -   1. creating a textured surface on the internal surfaces defining        the pores;    -   2. creating a microporous conduit system between pores;    -   3. reaction-extraction of endogenous growth factors;    -   4. carrying and/or delivering drugs, biologically active or        therapeutic agents;    -   5. function as a drug, biologically active or therapeutic agent;    -   6. modifying mechanical properties (e.g. strength, flexibility,        etc);    -   7. function as an in-vivo leachate to increase the overall        porosity.

The irregular pore surfaces formed by the modeling agent serves multiplepurposes, which may include but are not limited to:

-   -   1. increased surface area provides greater numbers of anchorage        points for cell attachment;    -   2. increased surface area permits modification to the leaching        rate of drugs or other therapeutics;    -   3. textured surfaces increase quantity of material that can be        coated on the interior pore surfaces;    -   4. irregular surfaces increase the resistance to flow through        the implant.    -   5. engineered surfaces can affect how cells attach, thereby        modifying the resulting tissue that is generated.    -   6. engineered or roughened surfaces can alter the overall pore        geometry, which can affect stresses on differentiating cells,        thereby dictating cell differentiation modalities.

Referring now to the drawings, wherein like reference characters referto like parts, one contemplated embodiment of the invention is shown inFIG. 1A. In this embodiment of a polymer tissue fixation device, theregular ordered pores 12 comprising the porous material of theprosthesis 10 is produced in the approximate shape required for use as abone plate implant for a patient. Similarly, as shown in FIG. 1B, theporous material of the device 10 is composed of random, irregular pores14. In either of these embodiments of the invention, where the device 10is to be utilized to stabilize a fissure created in the parietal boneduring the course of cranial surgery, a flat disk or rectangle shapemight suffice, as shown. The height of the disk would be such that whilefastened to the skull by any suitable means known in the art (e.g.,adhesives, clamps, medical staples, nails, pins, tacks, screws, sutures,or wires), the implant would not protrude markedly from the skull andwould allow replacement of the scalp to cover the implant. Similarly,the same implantable device might be used to cover a hole drilled or avoid cut in the parietal bone. Such an implant would not be subjected tohigh physical stresses, and can be manufactured in an appropriate mannerto create a more compliant plate, such that it is capable of complyingwith the curves of the skull surfaces.

The surgeon, prior to implantation, may customize the length, width, andshape of the implantable device. These alterations may include bending aspecific portion of the device, cutting to the desired size or shape, orpunching holes. Due to the porous nature of the implant, the alterationsmay be performed quickly by hand, or alternatively facilitated throughthe use of simple hand tools, for example a scalpel, scissors, a needleor an awl. In contrast, prior art metal bone plates are relativelydifficult to bend to a desired shape and are not capable of being cut orhave holes punched through directly before implanting in the patient.Similarly for the prior art non-porous polymer bone plates that requireheating to the glass transition temperature in order to be bent withoutcracking or breaking, and are also not capable of being cut or havingholes punched through just before use, as sharp edges, cracks ordistortion of the implant would occur. The porous structure of theinvention allows it to remain flexible over a wide range oftemperatures, ranging from below freezing and up to the melting point ofthe specific polymer or combination of polymers. This low temperatureflexibility allows the device to be simply and quickly bent or cut,contemporaneously with the ongoing procedure, therefore allowing theprocedure to be completed in less time, and reducing the risk of harm tothe patient. The physical characteristics of the subject invention aresuch that the surgeon has great flexibility in the customizationprocess, the placement of holes, modifications of shape and variousbends can easily be accomplished in manners not previously possible withprior art solid bone plates, whether metal or polymer. Additionally,should the surgeon choose, the porous polymer device could be heatedabove the glass transition temperature and preformed with greater easethan solid polymer devices due to the lower mass of the porousprosthesis, as compared to a solid prosthesis currently known in theart.

Referring again to FIG. 1A, a larger plate of the prosthetic materialcan be made, from which one or many different prosthetic devices 10 caneasily be cut, and in this manner, a single piece may be capable ofbeing shaped into several copies of the device 10, all which may then bealtered further, if necessary, and implanted into a living being. Thisallows the surgeon great flexibility in deciding what size bone platewould be required, and the general shape required. Furthermore, due tothe ease with which the plate material may be bent, and formed, thesurgeon is able to achieve a custom fit for each patient very quickly,and with little time spent forming the prosthesis to fit.

Referring to the prior art depicted by FIGS. 7A and 7B, the effects ofbending forces 80 (shown in orientation here by arrows) upon a solid,polymer bone fixation plate 75, as known in the prior art, is depictedin cross section. While at room temperature, and below the glasstransition temperature of the polymer, bending forces 80 may be appliedto the solid, polymer bone plate 75, however, due to the physicalcharacteristic of the solid implant, the solid, polymer implant mayflex, but will not readily conform to a different shape. Rather, asshown in FIGS. 7A and 7B, the plate 75 will either crack 77 or break 79.Contrast this now, with the porous material of the present invention, asdepicted in FIGS. 2A and 2B, wherein the polymer device 10 is capable ofbeing bent without requiring heating. A cross-sectional depiction of onepossible embodiment of the invention is depicted in FIG. 2A, whereindevice 10 is shown having regular ordered pores 12. FIG. 2B depicts thedevice 10 as it is being bent, wherein the bending force 80 is applied(shown in orientation here by arrows), causing the deformation andcollapse of pores in the region along the inside of the bend 22. Asdiscussed in further detail to follow, pores in the region on theoutside of the bend 24 may also undergo a shape or size change, althoughit may be a more subtle change compared to those on the inside of thebend. The collapsing of the pores along the inside of the bend 22 servesto distribute the bending force 80 applied over an area comprising aradius, thereby ensuring that the prosthetic device 10 bends smoothly,forming a radius curve 26, rather than cracking or breaking, as would asolid piece of material (the prior art depicted in FIG. 7A and 7B) withsimilar rigidity and without the porous construction 12 of theinvention. Furthermore, after the bending forces 80 are released, thecollapsed pores along the inside region of the bend 22 will not springback to their original shape 12, rather they will remain substantiallyin the deformed and collapsed state, thereby ensuring that the smoothbend forming a radius curve 26 in the prosthesis 10 remains after thebending forces 80 are removed. Though not shown, a similar deviceconstructed of random, irregular pores (as shown in FIG. 1B) wouldbehave similarly under the application of bending forces, forming asmooth radius curve by the collapse of pores along the inside region ofthe curve.

The collapsing of a porous layer along the inside of a bend permittingthe bending of a solid or nearly solid layer into radii previouslyunachievable without cracking or breaking can be seen by referring toFIGS. 8A and 8B. These figures depict a beam being bent in an arc. Inthe unbent condition (FIG. 8A), the upper and lower surfaces have thesame length, but in the bent condition (FIG. 8B), one can see that bothsurfaces are strained. In particular, the upper surface is distended orstretched, and the lower surface is shortened or compressed. This arisesbecause the upper and lower surfaces are connected to one another, andthey try to maintain their continuity after bending. Thus, the uppersurface is in a state of tensile stress, and the lower surface is in astate of compressive stress. Moreover, there is a region between theupper and lower surfaces that does not change in length, and this zoneis in a neutral stress state, being neither compressed nor in tension.One can also see from the bent beam of FIG. 8B that the sharper thebend, the smaller are the radii at the inner and outer surfaces, and thegreater the amount of strain (i.e., fractional change of length) thereis of these surfaces.

Consider now that the beam is porous, or at least porous at its upperand lower surfaces. The collapsing of pores on and near the lowersurface is a response to the compressive stress, and an accommodation ofthis stress since the material reacts to an externally applied stress insuch a way as to minimize internal stress. In other words, thecollapsing of pores at the lower surface reduces the amount ofcompressive stress. Similarly, the pores on and near the upper surfaceare under a tensile stress due to the bending, and can respond to thisstress by becoming more elongated in the tensile direction. Thiselongation is often accompanied by a shortening of the pore in adirection perpendicular to the tensile direction, i.e., a flattening ofthe pore, so this, too, can be thought of as a collapse of the pore.Because the compressive and tensile stresses must be in balance, therelaxation of stress at one surface, e.g., due to collapsing or pores,also causes a relaxation of stress at the opposite surface. Accordingly,the collapsing of pores permits amounts of bending that would otherwisecause cracking or breaking of the solid polymer in beams not having sucha porous layer.

Another way of looking at the stress and strain states in the bent beamis as follows. The bent beam would like to keep the upper and lowersurfaces the same length, so the left edge of the bent beam would berepresented by line c-d. But this it cannot do, since the upper surfaceis firmly connected to the bottom surface, so the left edge ends upbeing represented by line e-f. Thus, the bottom surface is shortened ascompressed pores collapse, and the upper surface is lengthened as poresin tension also collapse in a direction normal to the tension. Thecollapsing pores serve to relieve the compressive and tensile stresses,and thus relaxing the overall stress state of the material. Thisrelaxation allows the material to deform with lower stress, whencompared with non-porous materials.

Similarly, supplying a porous layer or section at or near an outersurface of an otherwise non-porous structure will allow stressrelaxation through the collapsing (or elongation) of the pores. Thisrelaxation will allow deformation at lower stresses, thereby allowingmore strain to be experienced before the critical breaking stress isreached.

FIG. 2C and 2D depict a cross-sectional view of another possibleembodiment of the device 10, comprising a porous layer 19 of orderedpores 12 and a layer of solid or nearly solid material 16. Thetransition from porous material 12 to a solid material 16 may be anabrupt transition 28 as depicted, or alternatively the transition may bea gradual transition that occurs as the size and population density ofthe pores decreases gradually in construction (not shown). Behavingsimilarly to the depictions of FIGS. 2A and 2B, the dual layerprosthesis of FIGS. 2C and 2D is capable of being smoothly bent, byforming a radius curve 26 when bending forces 80 are applied. In thedepiction of FIG. 2D, the pores 12 comprising the porous layer 19 alongthe inside of the bend 22 will collapse, and allow the formation of aradius in the solid or nearly solid layer 16 of material along theoutside of the bend 24; resulting in a smooth bend rather than crackingor breaking as would the prior art of FIGS. 7A and 7B. Though not shown,a device constructed from a dual layer device composed of a layer ofrandom, irregular pores and a solid or nearly solid layer would exhibitbending behavior similar to that shown by FIGS. 2C and 2D.

As a non-limiting example, the dual layer device 10 of FIG. 2C maycomprise a solid or nearly solid layer 16 of synthetic polymer (e.g.,PGA, PLA, etc.), and the regular, ordered porous layer 19 may be formedof a porous matrix of non-synthetic material (e.g., collagen, alginate,chitosan, etc.) Due to the nature of the materials utilized for thisparticular example, the porous layer 19 composed of non-syntheticmaterial, will, while dry, afford structural support to facilitate thebending of the solid layer 16, by selectively collapsing a portion ofthe pores 12. However, when wetted (e.g., after implantation, orexposure to a liquid or solvent), the layer of regular, ordered porousmaterial 19 comprised of non-synthetic material loses its rigidity andbecomes soft and compliant, or alternatively may quickly be dissolvedentirely, leaving only the synthetic solid or nearly solid layer 16 ofthe device 10, as the non-synthetic polymers are soluble in tissuefluids, or lose structural rigidity when wetted. The porous materiallayer may be composed of irregular random pores, and exhibit a similarbehavior, though this is not shown.

Due to the construction of the dual layer device of FIGS. 2C and 2D, thesmooth bending may occur causing the regular, ordered porous layer 19 toform the inside of the curve 22. As the bending forces 80 are applied,they cause the collapse of the regular, ordered pores 12, with thecollapsed pores distributing the bending forces 80 over a radius, thuspermitting the smooth bending of the solid or nearly solid layer 16.

As shown in FIGS. 2E and 2F, the multi-layer construction herein hasmore than two layers. In this embodiment, there is shown a solid ornearly solid layer 16, sandwiched between regular ordered porous layersabove 20 and below 21. Though it is recognized, but not shown, that theirregular, random pores would behave similarly. In this embodiment,bending forces 80 may be applied in either orientation, and as the pores12 are able to collapse and distribute the bending forces in eitherdirection, more elaborate multi-directional bends are possible, withoutbreaking the solid or nearly solid layer 16 as the bending forces 80would form radius curves 26, and with multiple curves may allow ‘s’bends or other types of bends.

A cross-sectional depiction of an alternate embodiment of the inventionis depicted in FIG. 3A. The prosthesis 10 of FIG. 3A features a laminarconstruction, which comprises a series of layers 31,32,33 of varyingpore sizes and pore densities. Though the depiction here is of regularordered pores 12, this is for ease of illustration, and may suitably beirregular, random pores. It is contemplated that the prosthesis 10 bemade entirely of one resorbable material, or alternatively, with each ofthe layers of the laminar construction 31, 32, 33 comprising the same ora different resorbable material. Furthermore, the prosthesis 10 of thisembodiment or any other of these embodiments may be fabricated by addingat least one reinforcing material to the prosthesis (to be discussedlater).

As shown in FIG. 3C, the varying pore sizes of the layers 31, 32, 33would offer varying resistance to collapse, with the larger pores oflayer 31, being more easily collapsed than the smaller pores of theintermediate layer 32, which in turn would be more easily collapsed thanthe even smaller pores of the smallest pore layer 33. It is recognizedthat in order for the existence of multi-layer construction, at leasttwo layers are needed. For ease of illustration, three distinct layersare depicted by FIGS. 3A, B, and C, but it is recognized that there maybe more or less layers. It is also recognized that the interface ortransition between the layers may be gradual or abrupt; for ease ofillustration, abrupt interfaces between the distinct layers aredepicted. It is also recognized that the distinction of layers may bebased upon some other characteristic than pore size, such as poredensity, material of construction, or some other identifiable quality,for ease of illustration, the distinction is made by pore size and poredensity.

This multi-layer construction depicted by FIG. 3C would allow bendingforces 80 to be applied (shown in orientation here by the large blackarrows) upon the device 10, with the resulting smooth bend in a radiuscurve 26 demonstrated by FIG. 3C. As a result of the laminarconstruction, incorporating differing layers having varying resistanceto collapsing of the pores, a more suitable bone plate may beconstructed, relative to a non-porous bone plate; yet the laminar porousconstruction will retain the ability to be smoothly bent to facilitatecustomization of the implant. This may be accomplished, for example, byreducing the pore sizes in the layer 33 along the outside of the bend24, resulting in greater strength in that layer 33, and at the sametime, increasing the pore sizes in the layer 31 along the inside of thebend 22, where additional flexibility is gained by the more easilycollapsed pores of the larger pore layer 31. In this manner, theprosthesis 10 is able to bend smoothly, forming a radius curve 26,rather than breaking as it would if the same bending force 80 (referringto the prior art of FIGS. 7A and 7B) was applied and absorbed by only asmall area, such as along a narrow crease in the fold or bend of thesolid plate 75.

Furthermore, when bending forces 80 are removed, the smooth bend of theradius curve 26 in the multi-layer device shown by FIG. 3C will remain,as the irreversibly collapsed pores along the inside region of the curve22 will not return to their original shape.

It is recognized that a great number of layers may be constructed intothe device, comprising various combinations distinguishable by theirnumber, structure, or other distinguishable characteristics; such as thestructural properties of the device may be altered by creating differentcombinations of layers, pore sizes, construction materials or otherstructural qualities.

A prosthesis constructed as shown in FIG. 3A would be able to conform tothe shape of an uneven surface, as depicted in FIG. 3B. This may beaccomplished by applying compressive force 81 (shown in orientation hereby arrows) upon the device 10, compressing the device evenly against anexposed uneven surface 36, with resistance 82 (shown in orientation hereby arrow) offered by the uneven surface 36 against the device 10. As aresult of the compressive force 81 and resistance 82, the initialresistance from the protruding areas 38 would selectively deform andcollapse the larger and more easily collapsed layer of pores 31, and toa lesser extent the intermediate pores of layer 32, the affected poreslocated proximally to the protrusion area 38, leaving the layers withsmaller pores 33 intact. Furthermore, the recessed areas 39 of theuneven surface 36 would not deform or collapse any of the pores in thelayers 31, 32, 33. As a result of the compressive force 81 and theresistance 82, affecting the pore structure of the device 10, theprosthesis surface may be altered to take on the inverse shape of theexposed surface 36, and therefore complies with the uneven surface 36.Upon removal of the compressive force 81, the device 10 will not springback elastically to the original shape due to the fact that a portion ofthe pores 12 had irreversibly collapsed.

Referring to FIG. 4, wherein a prosthesis 10 having random, irregularpores 14 is depicted, the prosthesis 10 with random pores 14 is capableof being used with fastening systems known in the art. Though not shown,an alternate embodiment of the device having regular ordered pores wouldsimilarly be capable of being used with fastening systems known in theart. These fastening systems may include adhesives (not shown), medicalstaples 42, pins (not shown), nails 44, tacks (not shown), screws 46, orclamps (not shown), among other suitable fastening devices.

In one embodiment, the prosthetic device 10 may be manufacturedincorporating a hole 40, or alternatively a plurality of holes (notshown), extending at least partially through the prosthesis 10, whichcould accommodate the use of a suitable fastening method, such as e.g.;screws 46 or nails 44, to fasten the implantable device 10 through apre-existing hole 40. Depending on the intended use of the prosthesis10, the hole 40 may be created during the manufacturing process.

Preferably, the surgeon would be able to further customize theimplantable device 10 by creating any number of needed holes 40 for theprocedure. This may be accomplished by use of a hole-punch device,alternatively by a scalpel, scissors, the use of a cutting blade, or byany means suitable to penetrate into and through the prosthesis. Thetool will displace and deform the porous structure it comes in contactwith, such as in separating the material in making a hole 40, leavingthe pores more distant from the tool intact. In this manner, a hole 40may be made in the prosthesis 10, without large-scale tearing orsplitting of the prosthesis, as only the pores closest to the tool wouldbe disturbed, and thereby limit the effect upon pores away from thetool. When used in this manner, the physician retains the flexibility tolocate the fastening points where, in the physician's judgment, they aremost appropriate, without requiring pre-manufactured fastening points inthe prosthesis 10.

Most preferably, the prosthetic device 10 may be put in place, andfastened without the use of pre-manufactured holes in the prosthesis.This allows the physician to simply fasten the prosthesis 10 by anysuitable means known in the art, such as by forcing a screw 46, nail 44or staple 42 through the implant, wherein the porous structure 14 of thedevice 10 limits the amount of large scale tearing that may occur, asonly the pores closest to the tool will be affected, leaving the rest ofthe device intact. When used in this manner, the physician hasflexibility to locate the fastening devices in situ, without needing toapproximate where the location needs to be created. As a result, therewould not be a need to fit the prosthesis 10 to the appropriate shape,and then make the holes away from the patient; rather the prosthesis 10could be fitted to shape, and while the prosthesis 10 is in place,simply fastened into location by any suitable fastening means known inthe art, without requiring the existence of a pre-existing hole 40. Asan alternative to the use of rigid fastening systems, such as screws 46or nails 44 to fasten the prosthesis 10, the porous structure of thedevice 10 with irregular pores 14, and also having regular ordered pores(not shown) is capable of being sutured 48 as shown in FIG. 4. Thesuture 48 may be non-resorbable, or preferably be of a resorbablenature, so that it may dissolve over time, along with the prosthesis 10.The porous structure is compatible with the use of a suture 48 as theporous structure of the device 10 will accommodate a needle by the poresseparating as the needle penetrates, whether through the entirethickness of the prosthesis, or merely through a portion of thethickness of the prosthesis. The porous structure of the device 10 isable to resist suture pull-through, as the pulling force exerted by thesuture may be distributed over a large number of pores. For this reason,the thread of the suture 48 will not easily rip through the structureand pull out. By use of a suture 48, the prosthetic device 10 may beattached to soft tissue, without requiring a pre-manufactured hole 40for suturing, or attachment of sutures before use.

Still another alternative fastening method relies on the use ofadhesives to attach the prosthesis in place (not shown). While usingadhesives, a portion of the pores along the surface will be in contactwith, and may absorb a portion of a liquid adhesive. As the adhesivesets, the prosthesis will be attached to the tissue. Suitable adhesivesinclude fibrin, polymer, or cyanoacrylate glue, as well as others knownto those skilled in the art. Such adhesives may be capable ofpenetrating into the porous material of the implantable device 10, withthe effect of multiplying the bonded surface area, thereby resulting ina bond stronger than would be available if merely the exposed outersurface of the implant was coated by the adhesive.

As shown in FIG. 5, a cross-sectional depiction of the device as acomposite 51, comprising the device as previously described, as well asfeaturing further additional materials 50. The depiction of FIG. 5 is ofa composite device 51 having random, irregular pore structure 14;however, it is recognized that the composite device 51 may have regularordered pore structure as well, and further containing additionalmaterial 50. In one embodiment, the additional materials 50 may be highmodulus strengthening components (e.g., polymers, ceramics ormetallics), where the high modulus material will affect the physicalcharacteristics of the composite prosthesis 51, such as increasing therigidity, strength, and toughness of the resulting structure. Thestrengthening agent may be in various forms (e.g., particulate, fiber,whisker, mesh, weave, knit, yarn, etc.). The additional material may beuniformly distributed throughout the entire composite prosthesis 51, oralternatively selectively incorporated to achieve a desired effect.

The same additional material 50 incorporated to achieve a desired effectupon the physical properties of the composite implantable device 51 mayalso affect its biologic properties. As an example, hydroxyapatite wouldnot only improve the strength of the implant, but also be capable of,for example, extracting endogenous growth factors from the host tissuebed while functioning as a microporous conduit facilitating movement ofinterstitial fluid throughout the isolated porosities of the device. Inanother embodiment, the additional materials 50 may alter the resorptionqualities of the resorbable porous material. Other non-limiting examplesof suitable materials that may be added to the prosthesis are listed inTable 2. TABLE 2 Examples of Materials Incorporated into the CompositeDevice in Accordance with the Present Invention Alginate Bone allograftor autograft Bone Chips Calcium Calcium Phosphate Calcium SulfateCeramics Chitosan Cyanoacrylate Collagen Dacron Demineralized boneElastin Fibrin Gelatin Glass (e.g.- Bio-Glass) Gold GlycosaminoglycansHydrogels Hydroxyapatite Hydroxyethyl methacrylate Hyaluronic AcidLiposomes Microspheres Natural Polymers Nitinol Oxidized regeneratedcellulose Phosphate glasses Polyethylene glycol PolyesterPolysaccharides Polyvinyl alcohol Radiopacifiers Salts Silicone SilkSteel (e.g. Stainless Steel) Synthetic polymers Thrombin TitaniumTricalcium phosphate

The additional material 50 can serve multiple purposes, which mayinclude, but are not limited to:

-   -   1. creating a textured surface on the internal surfaces defining        the pores;    -   2. creating a microporous conduit system between pores;    -   3. reacting-extracting of endogenous growth factors;    -   4. carrying and/or delivering drugs, biologically active or        therapeutic agents;    -   5. functioning as a drug, biologically active or therapeutic        agent;    -   6. modifying mechanical properties (e.g. strength, flexibility,        suture retention, etc.);    -   7. functioning as an in-vivo leachate to increase the overall        porosity.

The textured surface created by the additional material 50 additionallyserves multiple purposes that may include but are not limited to:

-   -   1. increased surface area permits modification to the leaching        rate of drugs or other therapeutics;    -   2. textured surfaces increase quantity of material that can be        coated on the interior pore surfaces;    -   3. irregular surfaces increase the resistance to flow through        the implant.

Additional materials 50 may also be used at the time of manufacture tocontrol the process output (e.g. plasticizers, surfactants, dyes, etc.)For example, processing the polymer with stearic agents will cause thethinning of matrix between the pores, which is most easily penetrable,or rapidly resorbing, following implantation. This will result in acomposite device 51 with high strength, and interconnected pores.

The additional materials 50 may lend some other desired property to thecomposite prosthesis 51, such as the capability of deliveringbiologically active agents, or of being radio-opaque, in order to allowimaging by x-ray or MRI techniques while the prosthesis is implanted orbeing implanted in the living being. The additional material 50 would becapable of being resorbed in the body, either at the same rate ofabsorption as the polymer or at a faster or slower rate of resorption.Should the prosthesis further contain biologically active agents, theymay be delivered slowly as the surrounding porous material is resorbed.The period of delivery of the biologically active agents from the devicemay be delayed and/or further extended by incorporating drug depots intothe composite prosthesis, such that the biologically active agents areslowly released into the body. Alternatively, if the biologically activeagents comprising the additional material 50 are easily dissolved,tissue fluids may be capable of leaching out the agents as the tissuefluids permeate the porous structure of the composite prosthesis 51.Examples of biologically active agents that may serve as the additionalmaterial 50 of the composite prosthesis 51 are listed in Table 3.

The additional material 50 may be in the form of microspheres.Microspheres can be made of a variety of materials such as polymers,silicone and metals. Biodegradable polymers are ideal for use increating microspheres for use in these embodiments (e.g., see thoselisted in Table 1). The release of agents from bioresorbablemicroparticles is dependent upon diffusion through the microspherepolymer, polymer degradation and the microsphere structure. Althoughmost any biocompatible polymer could be adapted for this invention, thepreferred material would exhibit in vivo degradation. It is well knownthat there can be different mechanisms involved in implant degradationlike hydrolysis, enzyme-mediated degradation and bulk or surfaceerosion. These mechanisms can alone or combined influence the hostresponse by determining the amount and character of the degradationproduct that is released from the implant. In the extracellular fluidsof the living tissue, the accessibility of water to the hydrolysablechemical bonds makes hydrophilic polymers (i.e. polymers that take upsignificant amounts of water) susceptible to hydrolytic cleavage or bulkerosion.

Several variables can influence the mechanism and kinetics of polymerdegradation. Material properties like crystallinity, molecular weight,additives, polymer surface morphology, and environmental conditions. Assuch, to the extent that each of these characteristics can be adjustedor modified, the performance of this invention can be altered. Thesemicrospheres, serving as the additional material 50 in the compositedevice 51, may further contain and/or deliver biologically active agentsfrom Table 3. TABLE 3 Examples with Some Types of Biological,Pharmaceutical, and other Therapies that can be Delivered via theComposite Device in Accordance with the Present Invention Adenoviruswith or without genetic material Angiogenic agents AngiotensinConverting Enzyme Inhibitors (ACE inhibitors) Angiotensin II antagonistsAnti-angiogenic agents Antiarrhythmics Anti-bacterial agents AntibioticsErythromycin Penicillin Anti-coagulants Heparin Anti-growth factorsAnti-inflammatory agents Dexamethasone Aspirin HydrocortisoneAntioxidants Anti-platelet agents Forskolin Anti-proliferation agentsAnti-rejection agents Rapamycin Anti-restenosis agents AntisenseAnti-thrombogenic agents Argatroban Hirudin GP IIb/IIIa inhibitorsAnti-virus drugs Arteriogenesis agents acidic fibroblast growth factor(aFGF) angiogenin angiotropin basic fibroblast growth factor (bFGF) Bonemorphogenic proteins (BMP) epidermal growth factor (EGF) fibringranulocyte-macrophage colony stimulating factor (GM-CSF) hepatocytegrowth factor (HGF) HIF-1 Indian hedgehog (Inh) insulin growth factor-1(IGF-1) interleukin-8 (IL-8) MAC-1 nicotinamide platelet-derivedendothelial cell growth factor (PD-ECGF) platelet-derived growth factor(PDGF) transforming growth factors alpha & beta (TGF-.alpha., TGF-beta.)tumor necrosis factor alpha (TNF-.alpha.) vascular endothelial growthfactor (VEGF) vascular permeability factor (VPF) Bacteria Beta blockerBlood clotting factor Bone morphogenic proteins (BMP) Calcium channelblockers Carcinogens Cells Stem cells Bone Marrow Blood cells Fat CellsMuscle Cells Umbilical cord cells Chemotherapeutic agents Ceramide TaxolCisplatin Paclitaxel Cholesterol reducers Chondroitin Clopidegrel (e.g.,plavix) Collagen Inhibitors Colony stimulating factors CoumadinCytokines prostaglandins Dentin Etretinate Genetic material GlucosamineGlycosaminoglycans GP IIb/IIIa inhibitors L-703,081Granulocyte-macrophage colony stimulating factor (GM-CSF) Growth factorantagonists or inhibitors Growth factors Autologous Growth FactorsB-cell Activating Factor (BAFF) Bovine derived cytokines CartilageDerived Growth Factor (CDGF) Endothelial Cell Growth Factor (ECGF)Epidermal growth factor (EGF) Fibroblast Growth Factors (FGF) Hepatocytegrowth factor (HGF) Insulin-like Growth Factors (e.g. IGF-I) Nervegrowth factor (NGF) Platelet Derived Growth Factor (PDGF) RecombinantNGF (rhNGF) Tissue necrosis factor (TNF) Tissue derived cytokinesTransforming growth factors alpha (TGF-alpha) Transforming growthfactors beta (TGF-beta) Vascular Endothelial Growth Factor (VEGF)Vascular permeability factor (UPF) Acidic fibroblast growth factor(aFGF) Basic fibroblast growth factor (bFGF) Epidermal growth factor(EGF) Hepatocyte growth factor (HGF) Insulin growth factor-1 (IGF-1)Platelet-derived endothelial cell growth factor (PD-ECGF) Tumor necrosisfactor alpha (TNF-.alpha.) Growth hormones Heparin sulfate proteoglycanHMC-CoA reductase inhibitors (statins) Hormones Erythropoietin ImmoxidalImmunosuppressant agents inflammatory mediator Insulin InterleukinsInterlukins Interlukin-8 (IL-8) Lipid lowering agents Lipo-proteinsLow-molecular weight heparin Lymphocites Lysine MAC-1 Morphogens Bonemorphogenic proteins (BMPs) Nitric oxide (NO) Nucleotides Peptides PR39Proteins Prostaglandins Proteoglycans Perlecan Radioactive materialsIodine - 125 Iodine - 131 Indium - 192 Palladium 103Radio-pharmaceuticals Secondary Messengers Ceramide Signal TransductionFactors Signaling Proteins Somatomedins Statins Stem Cells SteroidsThrombin Sulfonyl Thrombin inhibitor Thrombolytics Ticlid Tyrosinekinase Inhibitors ST638 AG-17 Vasodilator Histamine ForskolinNitroglycerin Vitamins E C Yeast

Therapy delivery may come from the pores 14 of the composite prosthesis51, as released from physical entrapment of the therapy impregnatedwithin the walls of the pores 14; it may come from material adsorbed orloosely adhering to the surface of enclosed pores 14 or interconnectedpores (not shown); or it may stay suspended within the pores 14 of thecomposite device 51 as implanted, awaiting contact with tissue fluidentering the pores 14. FIG. 5 depicts the composite prosthesis 51 havingirregular, random pores, it is recognized that a composite prosthesishaving regular, ordered pores and additional material would behavesimilarly.

It is recognized that each of the delivery modes could result indifferent delivery rates. That is, therapy may evolve more rapidly frominterconnected pores (not shown), than from isolated pores 14, which mayin-turn release therapy faster than any therapy delivered by the polymerconstituent (e.g., as it degrades).

In one embodiment, the therapy delivered via the additional material 50is co-mingled with the various other constituents and components priorto the processing. This allows for some concentration of the therapy toremain in the polymer constituent, while some of the same therapymigrates or precipitates into the porous region of the matrix. Anequilibrium phase diagram for the components and constituents wouldallow the tailoring of the concentration of therapy in each region(i.e., pore or polymer constituent), additionally, therapies with lowsolubility in either component will aid preferential placement oftherapy.

As shown in FIGS. 6A, an alternative embodiment of the compositeprosthesis 51 may also incorporate random fibers or whiskers 61 as theadditional material to add strength or another property to the compositeprosthesis 51. Alternatively, and as shown in FIG. 6B, the fibers may bearranged in a non-random pattern, such as a weave, knit or mesh, orscaffold 62. The patterned fibers 62 may be arranged in a single layerforming a two-dimensional sheet, or they may form a reinforcing scaffoldextending in three dimensions through the composite prosthesis 51. Thepatterned fibers 62 or the random fibers 61, may extend throughout theentirety of the composite prosthesis 51, or alternatively may be limitedto a particular portion or layer of the composite prosthesis 51, wheregreater strength or altered physical characteristic is desired.

The incorporation of random fibers 61 or a non-random pattern of fibers62 into the porous material of the composite prosthesis 51 may impartadditional shear strength to the implant, enabling it to further resistmechanical stresses imposed while implanted in the living being. Thefibers 61, 62 may also serve as an additional safety measure; upon theformation of a break or fault in the porous structure of the implant,the incorporated fibers would ensure that the entire prosthesis is ableto remain in place, preventing a loose piece of the implant from beingable to migrate within the being.

The random fibers or whiskers 61, or the non-random fibers 62,comprising the additional material may be biocompatible andnon-resorbable, or more preferably biocompatible and resorbable, suchthat as the porous material of the composite device 51 is absorbed bythe living being, the fibers 61, 62 are absorbed as well. Resorbablefibers comprising the additional material may be constructed frommaterials selected from table 1 above, a non-exhaustive list of some ofthe materials from which the resorbable prosthesis may be constructed.The fibers 61, 62 may be the same material or a different material fromthe porous material comprising the prosthesis. Depending on thematerials selected, the composite prosthesis 51 may be resorbed at thesame rate or a different rate from the incorporated fibers 61, 62.

The structure of the prosthesis may be manufactured in such a way thatthere is a layered appearance to the bone plate when viewed incross-section. This may be accomplished by methods commonly known in theart, such as: porosogen particulate leaching; blown gas methods; gasforming polymerizations; lyophilization; phase separation, as describedin U.S. Pat. No. 6,355,699 B1 (Vyakarnum), and U.S. patent applicationSer. No. 10/022182 (Bowman). Any of these methodologies may be utilizedto create a prosthesis entirely uniform in material, however, havinglayers with a variety of pore sizes and densities (not shown). Forexample, there may be a first layer of material that is relatively lessporous, transitioning through a first interface to a layer that isrelatively more porous, and transitioning through a second interface toa layer that is relatively less porous. By tailoring the manufacturingprocess, a great many variety of combinations may be constructed into aprosthesis.

In an embodiment of the practice of the current invention, the bendableporous fixation device can be machined, punched, or molded into anyconfiguration, such as an internal fixation device for use in surgicalrepair, replacement, or reconstruction of damaged bone in any area ofthe body (e.g. pelvis, orbital floor, palate, jaw, long bone, etc.).Internal fixation devices may be successfully employed for manyconditions and applications (e.g., orthopedic, spinal, maxillofacial,craniofacial, etc.). The devices may take on various forms, including,but not limited to, common forms such as sheets, disks, cups, tubes,rolls, blocks, cylinders or pads suitable for attachment to tissues. Inaddition to fixation of tissues, the bendable porous fixation device hasthe ability to retain graft material (e.g., ceramics, demineralized bonematrix, allograft bone chips, autograft bone chips, etc.) within alocation. For example, a fixation plate that is bent into a sleeve canbe used to prevent migration of graft material placed into a segmentaldefect of a long bone, and further provide protection and support formaintaining the proper gap in the segmental defect.

In another embodiment, the bendable porous fixation device containsreinforcing materials such as long threads, screens, meshes or otherfibers. The polymer making up the pores supports, confines, and locksthe reinforcing material within a spatial conformation. This retards thereinforcing material from migrating within or dissection from thefixation device. This can be used to alter mechanical properties (e.g.,compressive strength) of the construct. Additionally, the polymer mayimprove the biocompatibility of the reinforcing material (e.g., improvedcellular attachment or adhesion to a mesh). The reinforcing material maybe centered within the construct, located on or just below one or moresurfaces or interspersed throughout the entire construct.

In another embodiment, the pores of the bendable porous fixation deviceare used to control the location and delivery of biologically activeagents (e.g., growth factors, hormones, bone morphogenic proteins,drugs, cells, viruses, etc.) (see table 3). The biologically activeagents could be located within the polymer walls or supported within thepores making up the device. Additionally, the biologically active agentscould be mechanically or chemically attached or bonded to the polymer orsuspended within a hydration fluid located in the pores of the bendablefixation device. This hydration fluid may contain a soluble polymer thatsuspends or binds the biologically active agent. Additionally, thehydration fluid containing the soluble polymer may be removed leavingthe soluble polymer as a coating on the pore walls or microstructuresuspended within the pores.

In another embodiment, the polymer of the bendable porous fixationdevice is used to control the location and orientation of particulatecomponents compounded into the porous material (e.g., tricalciumphosphate, Hydroxylapatite, calcium sulfate, autologous bone graftmaterial, allograft bone matrix, polymers, microspheres, etc.). Thepolymer supports, confines, and locks the particulate components withina spatial conformation. This retards the particulate from migratingwithin or disassociating from the fixation device. The particulate canbe used to alter mechanical properties (e.g., compressive strength) ofthe construct

In another embodiment, the materials made by these various processes maybe cross-linked to impart improved characteristics such as: mechanicalstrength (e.g., suturablity, compression, tension, etc.), andbiodurability (e.g., resistance to enzymatic and hydrolytic degradation,etc.). This enhancement of characteristics may be accomplished using oneor more of several different cross-linking agents, or techniques (e.g.,thermal dehydration, EDC, aldehydes (e.g., formaldehyde, gluteraldehyde,etc.), natural cross-linking agents (e.g., genipin, proanthocyanidin,etc.). Each type of cross-linking agent/technique or combinationsthereof imparts diverse mechanical and biological properties on thematerial. These properties are created through the formation of uniquechemical bonds that stabilize the construct. This stabilization greatlyincreases the ability of the construct to hold a shape and conformation;thereby, preserving the interlaced relationship between the fibers.

Several of these bendable fixation embodiments may also be manufacturedin composite laminate form. That is, flat sheet or shaped embodimentsmay be affixed to additional sheets or other materials (e.g. solidplates, screws, screens, meshes, etc.), by pressing, gluing, stitchingor other fastening means known to those skilled in the art. Thesemacro-composites may be created having the respective characteristics ofeach of the component materials, thereby creating a single device havingbeneficial characteristics from each of the component materials. Forexample, a resorbable, osteoconductive, porous and flexible first layerof the device, which is enhanced by being constructed as a laminate witha second layer in the form of a high strength mesh affixed to onesurface of the first layer; thereby creating a flexible, yet highstrength device.

Thus since the invention disclosed herein may be embodied in otherspecific forms without departing from the spirit or generalcharacteristics thereof, some of which forms have been indicated, theembodiments described herein are to be considered in all respectsillustrative and not restrictive, by applying current or futureknowledge. The scope of the invention is to be indicated by the appendedclaims, rather than by the foregoing description, and all changes whichcome within the meaning and range of equivalency of the claims areintended to be embraced therein.

1. A bendable polymer tissue fixation device for implantation into aliving body, said polymer fixation device being arranged as a graftretainment device, said polymer fixation device comprising a highlyporous body, said porous body comprising at least one polymer and aplurality of pores, wherein said porous body is capable of beingsmoothly bent to conform to a tissue structure, with said bending atleast partially collapsing a portion of the pores to form a radiuscurve, said polymer fixation device being suitable for attachment totissue, and capable of being gradually resorbed by said living body. 2.A bendable polymer tissue fixation device for implantation into a livingbody, said polymer fixation device comprising a highly porous body andan additional material, said porous body comprising at least one polymerand a plurality of pores, wherein said porous body is capable of beingsmoothly bent, with said bending at least partially collapsing a portionof the pores to form a radius curve, said additional material comprisingat least one biologically active agent being arranged as a drug depotable to deliver said at least one biologically active agent over aperiod of time, said polymer fixation device being suitable forattachment to tissue, and capable of being gradually resorbed by saidliving body.
 3. A bendable polymer tissue fixation device forimplantation into a living body, said polymer fixation device beingarranged as a graft retainment device, said polymer fixation devicecomprising a composite, said composite comprising a highly porous bodyand at least one strengthening agent contained therein, said porous bodycomprising a plurality of pores and being capable of being smoothly bentto conform to a tissue structure, wherein said bending collapses aportion of the pores to form a radius curve, said polymer fixationdevice being suitable for attachment to tissue, and capable of beinggradually resorbed by said living body.
 4. A bendable polymer tissuefixation device for implantation into a living body, said polymerfixation device comprising a composite, said composite comprising ahighly porous body, at least one strengthening agent contained therein,and at least one biologically active agent, said porous body comprisinga plurality of pores and being capable of being smoothly bent, whereinsaid bending collapses a portion of the pores to form a radius curve,said at least one biologically active agent being arranged as a drugdepot able to deliver said at least one biologically active agent over aperiod of time, said polymer fixation device being suitable forattachment to tissue, and capable of being gradually resorbed by saidliving body.
 5. A device suitable for implantation into a living body,said device comprising a laminar body, said laminar body having at leasta first layer, at least a second layer, said first layer comprising ahighly porous form of a first material, said second layer comprising asecond material arranged as a laminate against at least a portion of asurface of said first layer, said first layer comprising a polymer; saidporous form comprising a plurality of pores, said laminar body beingcapable of being smoothly bent, wherein said bending collapses a portionof the pores of the porous form to prevent cracking or breaking of thenon-porous form, said device being suitable for attachment to tissue,and capable of being gradually resorbed by said living body.
 6. Thedevice of claim 5, wherein said second material is a polymer.
 7. Thedevice of claim 5, wherein said second material is a metal.
 8. Thedevice of claim 5, wherein said second material is fibrous.
 9. Thedevice of claim 5, wherein said second material is porous.
 10. Thedevice of claim 5, wherein said second layer is in a form selected fromthe group consisting of a plate, a screen, and a mesh.
 11. The device ofclaim 5, further comprising at least one additive component.
 12. Thedevice of claim 11, wherein said at least one additive component isdistributed uniformly throughout said device.
 13. The device of claim11, wherein said at least one additive component is distributed withinsaid pores of said device.
 14. The device of claim 11, wherein said atleast one additive component is distributed in a portion of said device.